Intratumoral dendritic cells and T cells predict survival in gastroenteropancreatic neuroendocrine neoplasms.

Clinical management of gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) remains challenging. We recently introduced FMS-like tyrosine kinase 3 ligand (FLT3LG) as a possible biomarker for a proinflammatory tumor microenvironment. Here, we put a spotlight on the quantitative assessment of classical dendritic cells (cDC) and T cells in the context of FLT3LG mRNA levels in a retrospective study on NET G2/ G3 and NEC of pancreatic and gastric origin. Abundance of cDC and T cells and their relevant subpopulations were determined by immunofluorescent staining and correlated with FLT3LG mRNA levels as well as clinical outcome. Immune cell counts attested highly variable infiltration densities. Samples with presence of cDC or high numbers of T cells exhibited increased FLT3LG expression. Abundance of cDC, defined as HLA-DR+CD11c+ cells with CLEC9a (cDC1) or CD1c (cDC2), as well as CD3+ T cell and CTL (CD8+ CD3+) numbers correlated with FLT3LG mRNA levels and predicted disease-specific survival. Combining FLT3LG and T cell counts further improved this prediction. Therefore, tumor-infiltrating cDC and T cells are prognostic markers in NET G2/ G3 or NEC and FLT3LG mRNA may serve as a simple to use biomarker for a quantitative estimate of their abundance, mandating prospective evaluation in the context of immune-targeted therapies.